The purposes of the proposed work are to examine the interrelationships between sodium and calcium ion movements across cardiac cell membranes and to evaluate the role these ionic interactions play in regulating cardiac contractility. Ion-selective ionophores, compounds capable of carrying ions across membranes, will be used to achieve controlled alterations of interacellular cation concentrations, without necessitating the modification of the composition of the extracellular medium or of tissue activity. Subsequent changes in cardiac movements will be observed by measurement of cellular ionic fluxes and contents and by monitoring electrical and mechanical function of the heart. Initial studies will be directed toward quantitation of the ionophore-induced ion fluxes. Later work will couple administration of the ionophore with physiological and pharmacological inotropic interventions, such as altered rates of stimulation and cardiac glycosides in order to investigate the cellular locations and characteristics of sodium-sensitive Ca ions movements. These experiments will be conducted on a comparative basis, utilizing cardiac tissues from cats, rats and rabbits. Information acquired from these investigations will be applied to investigations of drug-induced alterations of cardiac contractility. In addition, the results of this work may have application to the control of other cellular systems, which exhibit similarities with the cardiac contractile process, such as those involved in excitation-secretion coupling.